Hydrogel composition for measuring glucose flux

Abstract

The present invention relates to compositions for use in analyte monitoring devices. These compositions are useful to increase the flux of analyte across skin, tissue or mucosal surfaces. The compositions include hydrogels and collection reservoir systems comprising ionically conductive materials. The present invention also includes methods of making / manufacturing hydrogels or collection reservoir systems, collection assemblies comprising the hydrogels, electrode assemblies in combination with the hydrogels or collection reservoir systems, and methods of using the same.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Application Ser. No. 60 / 404,807, filed 19 Aug. 2002, which application is herein incorporated by reference in its entirety.TECHNICAL FIELD[0002]The present invention relates generally to compositions and methods for the enhancement of transdermal analyte flux.BACKGROUND OF THE INVENTION[0003]A number of diagnostic tests are routinely performed on humans to evaluate the amount or existence of substances present in blood or other body fluids. These diagnostic tests typically rely on physiological fluid samples removed from a subject, either using a syringe or by pricking the skin. One particular diagnostic test entails self-monitoring of blood glucose levels by people with diabetes.[0004]Diabetes is a major health concern, and treatment of the more severe form of the condition, Type 1 (insulin-dependent) diabetes, requires one or more insulin injections per day. Insulin controls utiliz...

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Benefits of technology

[0166]A further advantage of the present invention is the possibility of reducing skin irritation. Analyte sensitivity (i.e., the amount of analyte detected after extraction) is improved when using the hydrogels of the present invention relative to hydrogels using lower concentrations of phosphate buffer (i.e., less than or equal to about 100 mM phosphate buffer concentration). This improved analyte sensitivity appears to be in large part due to increased transdermal flux of the analyte when using the hydrogels of the present invention. The higher flux of analyte across, for example, the stratum corneum, allows for using a lower current density to get a suitable flux of analyte to provide an adequate amount of analyte for detection / sensing. Use of a lower current for analyte extraction helps to reduce skin irritation at the site of contact of the device and the subject being monitored.

[0167]Accordingly, in one aspect of the present invention, higher concentrations of phosphate buffer in a collection reservoir, for example, a hydrogel, can assist in reducing skin irritation.2.5.4 Mutarotation

[0168]When the analyte of interest has two or more stereoisomeric forms, such as the anomeric forms of sugars which undergo mutarotation, and only one isomeric form of the analyte is detectable using a detection system, for example, electrochemical detection, then components may be added to the hydrogel to facilitate mutarotation to the detectable stereoisomeric form. This applies, for example, to sugars including but not limited to glucose.

[0169]For example, an aqueous solution of glucose contains α-glucose and β-glucose in an equilibrium. However, glucose oxidase is specific for β-glucose. Therefore, as the reaction proceeds, the concentration of β-glucose decreases and α-glucose mutarotates to maintain the equilibrium. The gradual mutarotation of α-glucose to β-glucose is manifested by delayed hydrogen peroxide formation, which may be carried over into the next measurement cycle. The purpose of increasing the mutarotation rate is to prevent the carryover of glucose to the next measurement cycle and to provide more accurate detection of glucose levels in a sample (e.g., including glucose originally present in the sample as both α-glucose to β-glucose). Carryover refers to the observation that not all glucose reacts within each measurement cycle. Thus, glucose can accumulate over time thereby decreasing the accuracy of results obtained in measurements occurring in later measurement cycles.

[0170]In addition, because a solution of glucose at equilibrium contains greater than 35% α-glucose, the signal with slow mutarotation is up to 35% lower than a signal from a sample with rapid mutarotation. More rapid mutarotation increases the signal to noise ratio.

[0171]Because a solution of glucose at equilibrium contains greater than 35% α-glucose, sensing times greater than 5 minutes may be required solely to determine the charge at the end of the reaction. Thus, an increased mutarotation rate is desirable because it (i) results in higher current values over a shorter measurement time period, (ii) results in higher signal to noise ratios, and (iii) reduces the recovery time thereby increasing the number of readings that can be taken over a given time interval.

Problems solved by technology

On the other hand, improper administration of insulin therapy can result in hypoglycemic episodes, which can cause coma and death.

However, the pain and inconvenience associated with this blood sampling, along with the fear of hypoglycemia, has led to poor patient compliance, despite strong evidence that tight control dramatically reduces long-term diabetic complications.

In fact, these considerations can often lead to an abatement of the monitoring process by the diabetic.

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